7U2Q
Influenza Neuraminidase N1-CA09-sNAp-155
Summary for 7U2Q
| Entry DOI | 10.2210/pdb7u2q/pdb |
| EMDB information | 26318 26319 |
| Descriptor | Influenza N1-CA09-sNAp-155, 2-acetamido-2-deoxy-beta-D-glucopyranose (2 entities in total) |
| Functional Keywords | influenza, antigen, engineered protein, structural genomics, seattle structural genomics center for infectious disease, ssgcid, viral protein |
| Biological source | Influenza A virus |
| Total number of polymer chains | 4 |
| Total formula weight | 171767.76 |
| Authors | Acton, O.J.,Veesler, D.,Seattle Structural Genomics Center for Infectious Disease (SSGCID) (deposition date: 2022-02-24, release date: 2022-04-20, Last modification date: 2024-10-23) |
| Primary citation | Ellis, D.,Lederhofer, J.,Acton, O.J.,Tsybovsky, Y.,Kephart, S.,Yap, C.,Gillespie, R.A.,Creanga, A.,Olshefsky, A.,Stephens, T.,Pettie, D.,Murphy, M.,Sydeman, C.,Ahlrichs, M.,Chan, S.,Borst, A.J.,Park, Y.J.,Lee, K.K.,Graham, B.S.,Veesler, D.,King, N.P.,Kanekiyo, M. Structure-based design of stabilized recombinant influenza neuraminidase tetramers. Nat Commun, 13:1825-1825, 2022 Cited by PubMed Abstract: Influenza virus neuraminidase (NA) is a major antiviral drug target and has recently reemerged as a key target of antibody-mediated protective immunity. Here we show that recombinant NAs across non-bat subtypes adopt various tetrameric conformations, including an "open" state that may help explain poorly understood variations in NA stability across viral strains and subtypes. We use homology-directed protein design to uncover the structural principles underlying these distinct tetrameric conformations and stabilize multiple recombinant NAs in the "closed" state, yielding two near-atomic resolution structures of NA by cryo-EM. In addition to enhancing thermal stability, conformational stabilization improves affinity to protective antibodies elicited by viral infection, including antibodies targeting a quaternary epitope and the broadly conserved catalytic site. Stabilized NAs can also be integrated into viruses without affecting fitness. Our findings provide a deeper understanding of NA structure, stability, and antigenicity, and establish design strategies for reinforcing the conformational integrity of recombinant NA proteins. PubMed: 35383176DOI: 10.1038/s41467-022-29416-z PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.2 Å) |
Structure validation
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